Clinical and Interpretive

Measurement of phenobarbital is useful for monitoring for appropriate therapeutic concentration and assessing compliance or toxicity.

Phenobarbital is a general central nervous system (CNS) suppressant that has proven effective in the control of generalized and partial seizures. It is frequently coadministered with phenytoin for control of complex seizure disorders and with valproic acid for complex parietal seizures.

Phenobarbital is administered in doses of 60 to 300 mg/day in adults or 3 to 6 mg/kg/day in children.

Phenobarbital is slowly but completely absorbed, with bioavailability in the range of 100%. It is approximately 50% protein bound with a volume of distribution of 0.5 L/kg. Phenobarbital has a long half-life of 96 hours, with no known active metabolites.

Sedation is common at therapeutic concentrations for the first 2 to 3 weeks of therapy, but this side effect disappears with time.

Toxicity due to phenobarbital overdose is characterized by CNS sedation and reduced respiratory function. Mild symptoms characterized by ataxia, nystagmus, fatigue, or attention loss, occur at blood concentrations >40 mcg/mL. Symptoms become severe at concentrations ≥60 mcg/mL. Toxicity becomes life-threatening at concentrations >100 mcg/mL. Death usually occurs due to respiratory arrest when pulmonary support is not supplied manually.

There are no known drug interactions that significantly affect the pharmacokinetics of phenobarbital; conversely, phenobarbital affects the pharmacokinetics of other drugs significantly because it induces the synthesis of enzymes associated with the hepatic cytochrome P450 metabolic pathway.

Acute intermittent porphyria attacks may be induced by phenobarbital stimulation of hepatic cytochrome P450.

Clinical response to the drug correlates strongly with blood concentration. Dosage adjustments are made after 2 weeks of therapy to achieve steady-state blood levels in the range of 20 to 40 mcg/mL for adults; 15 to 30 mcg/mL for infants and children. Patients chronically administered phenobarbital usually do not experience sedation unless the blood concentration is >40 mcg/mL.